This invention relates generally to medical devices and, particularly, to medical devices that are implantable either partly or completely into a human or veterinary patient.
It has become common to treat a variety of medical conditions by introducing an implantable medical device partly or completely into the esophagus, trachea, colon, biliary tract, urinary tract, vascular system or other location within a human or veterinary patient. For example, many treatments of the vascular system entail the introduction of a device such as a stent, a catheter, a balloon, a wire guide, a cannula, or the like. However, when such a device is introduced into and manipulated through the vascular system, the blood vessel walls can be disturbed or injured. Clot formation or thrombosis often results at the injured site, causing stenosis or occlusion of the blood vessel. Moreover, if the medical device is left within the patient for an extended period of time, a thrombus often forms on the device itself, again causing stenosis or occlusion. As a result, the patient is placed at risk of a variety of complications, including heart attack, pulmonary embolism, and stroke. Thus, the use of such a medical device can entail the risk of precisely the problems that its use was intended to ameliorate.
Another problem associated with implantable medical devices and, more particularly, to partly implanted medical devices such as catheters percutaneously introduced into the vascular system of a patient for long-term hemodialysis or drug infusion is the risk of infection. This risk is also present with hyperalimentation (intravenous feeding) catheters which are percutaneously introduced into the patient. The urinary tract is another system of the patient in which an urethral catheter such as a well-known Foley catheter is introduced into the patient""s bladder via the urethra for the drainage of urine.
A recent attempt to reduce the risk of infection has been to coat the outer surface of the device with a bioactive material and/or pharmacologically active ingredient such as an antibiotic. Various coatings including antibiotics have been utilized, but have been found to disperse or dissipate from the coating in a relatively short period of time. Although effective in short-term implantation, such coatings are typically ineffective for extended duration placement such as with hemodialysis, drug infusion, or urinary tract catheters, which can be implanted in the patient for two to three years at a time.
The applicant has tested a partly implantable device containing an inner, elongated tube with an elongated outer sheath coaxially positioned around the inner tube, and with an intermediate space established between them. A mixture of drugs having different diffusion rates through the sheath and tube were positioned such as by injection, into the intermediate space. It was found that the higher diffusion rate drug quickly diffused through the inner tube and outer sheath without the benefit of the lower diffusion rate drug therewith for concomitantly combating the risk of infection.
The present invention is intended to provide a device in which at least two treatment materials reach the external or outer surfaces simultaneously. The implantable or partly implantable medical device includes a first elongated member or tube and a second elongated member or tube positioned adjacent to or within the first member or tube. A pharmacologically active ingredient is positioned between and in communication with the first and second elongated members. At least one of the first and second elongated members is permeable to the pharmacologically active ingredient for diffusing the pharmacologically active ingredient therethrough. A bioactive material preferably with a base material such as of at least one of the first and second elongated members is also provided, and the selected member(s) is permeable to the bioactive material for diffusing the bioactive material therefrom or therethrough.
When the pharmacologically active ingredient material includes a mixture of ingredients, the bioactive material can advantageously include one of the slower diffusion rate ingredients of the mixture, which is included in the base material of the selected member(s). This slower diffusion rate ingredient is then advantageously more readily accessible to the tissue surrounding the device for concomitant treatment with the other higher diffusion rate ingredient(s) of the mixture.
By way of example, the pharmacologically active ingredient advantageously and preferably includes a mixture of minocycline and rifampin, which is positioned between and in communication with the first and second elongated members of the implantable medical device. Minocycline has a lower diffusion rate than that of rifampin, and as a result, is included as the bioactive material in the base material in either one or both of the first and second elongated members. The higher diffusion rate rifampin permeates through the permeable base material of the elongated members and is diffused with the lower diffusion rate minocycline for concomitant treatment of tissue surrounding the outer surface of the catheter.
The thickness of the base material is advantageously selected to, in effect, slow down the diffusion of the higher diffusion rate ingredient so that the higher and lower diffusion rate ingredients are diffused from the medical device concomitantly for treatment of the tissues surrounding the device.
In one aspect of the invention, the implantable medical device includes a catheter having an outer elongated member with a passage extending longitudinally therein and an inner elongated member defining a passage extending longitudinally therein bounded by an inwardly directed surface of the inner elongated member, defining a lumen. The inner member is positioned in the passage of and surrounded by the outer elongated member, thus defining an intermediate region between the inner and outer elongated members. A pharmacologically active ingredient such, as minocycline, rifampin, or a mixture thereof is positioned in the intermediate region. As a result, the pharmacologically active ingredient is positioned between and in communication with the outer and inner elongated members. At least one of the outer and inner members, and preferably the outer member, is permeable to the pharmacologically active ingredient.
Applicant""s improvement comprises including or mixing a bioactive material in the base material in at least one of the outer and inner members, which is permeable for diffusing therefrom or therethrough the bioactive material and/or the pharmacologically active ingredient from the intermediate space. The bioactive material can advantageously include the slower diffusion rate ingredient such as minocycline or pharmacologically active ingredient mixture.
In a preferred embodiment of the invention, the base material of the outer and inner members is silicone having a durometer in a range of 30 to 90 on the Shore A Hardness Scale. Preferably, the base material silicone has a durometer of 65 and is formed from a powder mixture with 7% minocycline by weight. A pharmacologically active ingredient such as a 50:50 mixture by weight of rifampin and minocycline is position in the intermediate region between the outer and inner coaxial members.
In another aspect of this invention, the intermediate region may comprise an elongated member or layer having a base material and that is positioned between the outer and inner elongated members, and the 50:50 mixture by weight of rifampin and minocycline is included or mixed with a base material of an intermediately positioned member or layer to a concentration of 7% by weight. The base material of the intermediately positioned member or layer can also include silicone, which is readily positioned or formed with the outer and inner coaxially positioned members. Advantageously, the outer member is in contact with the tissue of the patient of which fluid from the patient permeates through the catheter for diffusing the pharmacologically active ingredient and/or the bioactive material from the catheter.
In the preferred embodiment of the invention, an inner elongated member tube comprises a base material of silicone having 7% by weight minocycline included therein. An intermediate member or layer is positioned or formed over the inner member tube. The intermediate member or layer preferably includes a base material such as silicone and a 7% by weight mixture of 50:50 rifampin and minocycline. The outer elongated member tube also preferably comprises a base material of, for example, silicone and 7% by weight minocycline, which is positioned over the intermediate layer and inner member tubes. The overall wall thickness of the catheter is approximately one-quarter of that of the outside diameter of the catheter. As a result, the passage or lumen of the catheter is approximately one-half of its outside diameter. The wall thickness of the inner and outer elongated member tubes or layers is approximately the same, whereas the thickness of the intermediate layer is approximately two and one-half times that of either the inner or outer elongated member tubes or layers. The outside diameter of the preferred catheter falls within a range of 3 French to 18 French (0.039xe2x80x3 to 0.236xe2x80x3).